We have attempted to identify the transmitter of the perforant path input to the dentate gyrus and using this information study the mechanism of short term plasticity. Our studies indicate that glutamate is the transmitter. Studies using a glutamate antagonist suggest that long term potentiation involves a change in postsynaptic excitability. We are presently continuing to define the mechanism of long and short term plasticity in the dentate gyrus using various drugs which interfere with glutamatergic synaptic transmission. We have also continued our studies on lesion induced synaptogenesis in the dentate. We have discovered that serial lesions accelerate axon sprouting so that it occurs 3 to 4 times faster. We have also found that interference with axonal flow will induce the formation of additional synapses within the affected area. These data suggest that negative neurotrophic substances regulate, in part, the proliferation of terminal field in the dentate gyrus. We are continuing studies on serial lesions to determine if the onset of function is accelerated along with the growth of new axons.